Depressive symptoms can be a common problem in women during the transition to menopause. Studies have shown that, in certain settings, major depressive disorders are more common in perimenopausal women than in the general population. Community-based studies have found that while some women are at increased risk for mood disorders during this period, they may not be at an increased risk for major depressive disorders during this time. Multiple studies have been inconsistent with regard to the impact of estrogen replacement therapy (ERT) on depression in perimenopausal women. Soares and colleagues studied the efficacy of 17β-estradiol in the treatment of depression in women who were confirmed to be perimenopausal.

The participants in the study were perimenopausal women who were 40 to 55 years of age with irregular periods and serum follicle-stimulating hormone levels greater than 25 mIU per mL (25 IU per L). In addition, the participants had to meet criteria for major depressive disorder, dysthymic disorder, or minor depressive disorder based on standards in Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). Those who qualified for the study were randomly assigned to receive transdermal patches of 17β-estradiol (100 mg) or placebo for 12 weeks in a double-blinded, placebo-controlled study. A four-week washout period followed the 12-week treatment phase. The main outcome measures were assessed using the Montgomery-Åsberg Depression Rating Scale and the Blatt-Kupperman Menopause Index scores.

Results of the study showed that 68 percent of the women receiving ERT had a remission of their depression, which was a significant difference when compared with the placebo-control group. Women who received ERT also had similar results in all three DSM-IV diagnoses. The positive effect of ERT was noted even at the end of the four-week washout period, although somatic complaints increased in frequency and intensity at this time. The adverse events were mild for ERT and placebo groups, and only one ERT participant had to drop out of the study secondary to an increase in migraine headaches.

The authors conclude that transdermal estrogen replacement is an effective antidepressant treatment in perimenopausal women with depressive disorders. This treatment was equally effective in women who did and women who did not have vasomotor symptoms before the start of the study. The authors add that ERT has a potential role in the treatment of perimenopausal mood disorders. Larger clinical trials with a longer treatment follow-up period are needed.